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General Information
Voydeya (danicopan) is a complement factor D inhibitor.
Voydeya is specifically indicated as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH).
Dosing/Administration
Voydeya is supplied as tablets for oral administration.
Recommended Vaccination and Prophylaxis for Encapsulated Bacterial Infections
- Vaccinate patients against encapsulated bacteria, including Neisseria meningitidis (serogroups A, C, W, Y, and B) and Streptococcus pneumoniae according to current ACIP recommendations at least 2 weeks prior to initiation of Voydeya.
- If urgent Voydeya therapy is indicated in a patient who is not up to date with vaccines for Neisseria meningitidis and Streptococcus pneumoniae according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.
- Healthcare professionals who prescribe Voydeya must enroll in the VOYDEYA REMS
Recommended doses:
Starting Dose:
The recommended dosage of Voydeya is 150 mg three times a day administered orally. Voydeya can be taken with or without food.
Dose Adjustment:
The dose can be increased to 200 mg three times a day if the patient’s hemoglobin (Hgb) level has not increased by greater than 2 g/dL after 4 weeks of therapy, if the patient required a transfusion during the previous 4 weeks, or to achieve an appropriate Hgb response based on clinical judgement.
Missed Doses:
A patient who misses a dose of Voydeya
should take it as soon as they remember unless it is within 3 hours prior to
their next dose, in which case the patient should skip the missed dose and take Voydeya
at the next regularly scheduled
time. Patients should not take two or more doses of Voydeya
at the same time.
Mechanism of Action
Voydeya (danicopan) binds reversibly to complement Factor D and selectively inhibits the alternative complement pathway. Danicopan prevents the cleavage of complement Factor B into the Ba and Bb fragments which are required for the formation of the alternative pathway (AP) complement component C3 convertase (C3bBb), the generation of downstream effectors including C3 fragment opsonization, and the amplification of the terminal pathway. In PNH, intravascular hemolysis (IVH) is mediated by the terminal membrane attack complex (MAC), while extravascular hemolysis (EVH) is facilitated by C3 fragment opsonization. Danicopan acts proximally in the alternative pathway of the complement cascade to control preferentially C3 fragment-mediated EVH, while co-administered ravulizumab or eculizumab is anticipated to maintain control over MAC-mediated IVH.
Side Effects
The most frequent adverse effect associated with the use of Voydeya was headache.
The Voydeya drug label comes with the following Black Box Warning: Voydeya increases the risk of serious and life-threatening infections, caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B. Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of Voydeya, unless the risks of delaying Voydeya outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor. Patients receiving Voydeya are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected. Voydeya is available only through a restricted program called VOYDEYA REMS.
Clinical Trial Results
FDA approval of Voydeya was based on the pivotal Phase III ALPHA trial designed as a superiority study to evaluate the efficacy and safety of danicopan as an add-on to C5 inhibitor therapy eculizumab or ravulizumab in patients with PNH who experience clinically significant EVH. In the double-blind, placebo-controlled, multiple-dose trial, patients were enrolled and randomized to receive danicopan or placebo (2:1) in addition to their ongoing eculizumab or ravulizumab therapy for 12 weeks. A prespecified interim analysis was performed once 63 randomized patients had completed 12 weeks of the primary evaluation period or discontinued treatment as of June 28, 2022. At 12 weeks, patients on placebo plus a C5 inhibitor were switched to danicopan plus eculizumab or ravulizumab, and patients on danicopan plus eculizumab or ravulizumab remained on treatment for an additional 12 weeks.
At the prespecified interim analysis for the ALPHA trial danicopan met the primary efficacy endpoint. In patients managing PNH with eculizumab or ravulizuma, add-on treatment with danicopan was superior to placebo plus eculizumab or ravulizumab based on change in haemoglobin from baseline to week 12, reported as least squares mean change from baseline and standard error of the mean (2.94 [0.211] g/dL vs 0.50 [0.313] g/dL; p<0.0001). Further, significant improvements in hemoglobin were observed with danicopan by week 2 and maintained through week 12.
All key secondary endpoints also met statistical superiority in favor of danicopan plus eculizumab or ravulizuma, compared to placebo plus C5 inhibition. Results showed significantly more patients treated with danicopan (59.5%) versus placebo (0%) experienced an improvement in hemoglobin of ≥2 g/dL at week 12 in the absence of transfusion (difference in danicopan-placebo: 46.9, 95% CI: 29.2–64.7, p<0.0001).
Additionally, significantly more patients treated with danicopan avoided transfusion (remaining transfusion-free and not requiring a transfusion as per protocol) through week 12, versus the comparator arm.